Different angiogenic pathways in human cervical cancers.
OBJECTIVE
The objective of this study is to clarify the association between the expression of two types angiogenic factors, vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase(dThdPase) and clinicopathological features, including tumor angiogenesis, in cervical cancers.


METHODS
The expression of VEGF and PD-ECGF was evaluated by immunohistochemical staining of tumor specimens from 73 patients with stage Ib-IIb cervical cancer (51, squamous cell carcinoma; 19, adenocarcinoma; 3, adenosquamous carcinoma) who underwent radical hysterectomy. The microvessel density was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area.


RESULTS
The microvessel density in adenocarcinomas was significantly higher than that in squamous cell carcinomas (P < 0.01). The intensity of VEGF expression in adenocarcinomas was significantly stronger than that in squamous cell carcinomas (P < 0.05). In contrast, the expression of PD-ECGF in squamous cell carcinomas was significantly higher than that in adenocarcinomas (P < 0.0001) and adenosquamous carcinomas (P < 0.01). There was an inverse relationship between VEGF expression and PD-ECGF expression among all patients studied (P < 0.001). The microvessel density was significantly correlated with the intensity of VEGF expression (P < 0.05). In contrast, there was no correlation between the microvessel density and the expression of PD-ECGF.


CONCLUSIONS
The expression of VEGF appears to be involved in the promotion of angiogenesis in cervical cancers. Furthermore, we propose that angiogenic pathways may be different in different types of cervical cancers.
Tokumo
K
K
Department of Obstetrics and Gynecology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama, 700, Japan.
Kodama
J
J
Seki
N
N
Nakanishi
Y
Y
Miyagi
Y
Y
Kamimura
S
S
Yoshinouchi
M
M
Okuda
H
H
Kudo
T
T
D000230:Adenocarcinoma / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D018196:Carcinoma, Adenosquamous / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008222:Lymphokines / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D008833:Microcirculation; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D013939:Thymidine Phosphorylase / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000032:analysis / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor; D013939:Thymidine Phosphorylase